Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; State Key Laboratory of Supramolecular Structure and Materials and Institute of Theoretical Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, PR China.
Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Mol Cell Endocrinol. 2019 Jun 1;489:107-118. doi: 10.1016/j.mce.2018.11.012. Epub 2018 Nov 30.
17β-Hydroxysteroid dehydrogenases (HSD17B) catalyze the oxidation/reduction of 17β-hydroxy/keto group in position C17 in C18- and C19 steroids. Most HSD17Bs are also catalytically active with substrates other than steroids. A subset of these enzymes is able to process thioesters of carboxylic acids. This group of enzymes includes HSD17B4, HSD17B8, HSD17B10 and HSD17B12, which execute reactions in intermediary metabolism, participating in peroxisomal β-oxidation of fatty acids, mitochondrial oxidation of 3R-hydroxyacyl-groups, breakdown of isoleucine and fatty acid chain elongation in endoplasmic reticulum. Divergent substrate acceptance capabilities exemplify acquirement of catalytic site adaptiveness during evolution. As an additional common feature these HSD17Bs are multifunctional enzymes that arose either via gene fusions (HSD17B4) or are incorporated as subunits into multifunctional protein complexes (HSD17B8 and HSD17B10). Crystal structures of HSD17B4, HSD17B8 and HSD17B10 give insight into their structure-function relationships. Thus far, deficiencies of HSD17B4 and HSD17B10 have been assigned to inborn errors in humans, underlining their significance as enzymes of metabolism.
17β-羟甾脱氢酶（HSD17B）催化 C17 位 C18 和 C19 甾类化合物 17β-羟基/酮基的氧化/还原。大多数 HSD17B 对除甾体以外的底物也具有催化活性。这些酶中的一部分能够处理羧酸的硫酯。这组酶包括 HSD17B4、HSD17B8、HSD17B10 和 HSD17B12，它们在中间代谢中执行反应，参与脂肪酸的过氧化物体β-氧化、3R-羟酰基的线粒体氧化、异亮氨酸的分解和内质网中脂肪酸链的延伸。不同的底物接受能力体现了在进化过程中获得催化位点适应性。作为一个额外的共同特征，这些 HSD17B 是多功能酶，它们要么通过基因融合（HSD17B4）产生，要么作为亚基整合到多功能蛋白复合物中（HSD17B8 和 HSD17B10）。HSD17B4、HSD17B8 和 HSD17B10 的晶体结构提供了它们结构-功能关系的深入了解。到目前为止，HSD17B4 和 HSD17B10 的缺乏已被归因于人类的先天性错误，强调了它们作为代谢酶的重要性。
